Vancomycin is used to treat serious infections of methicillin-resistant staphylococci. Vancomycin is produced by cultivating the bacteria S. orientalis in a nutrient culture media.
The vancomycin broth is filtered and added to a column that contains an adsorption resin that decolorizes and desalts the vancomycin. The resin is washed, and the vancomycin eluted with a solvent of low pH, followed by decolorization with carbon.
The vancomycin eluant is then further purified using a single recrystallization step at low pH. The crystallized vancomycin is combined with a strong acid such as hydrochloric acid (HCl) and precipitated in an organic solvent such as acetone to form vancomycin.HCl. This process for the manufacture and purification of vancomycin HCl is disclosed in U.S. Pat. No. 3,067,099 to McCormick et al.
In another example of a prior art process for the manufacture of vancomycin.HCl, a solvent of 0.1% phosphoric acid (H.sub.3 PO.sub.4) in a solution of 10% isopropyl alcohol (IPA) is used to elute purified vancomycin from the adsorption column. The vancomycin eluant is then concentrated using reverse osmosis or vacuum evaporation. An aqueous solution that contains approximately 60 g/l of potassium phosphate (KH.sub.2 PO.sub.4) is added to the concentrated vancomycin solution. The KH.sub.2 PO.sub.4 causes the vancomycin to crystallize from the solution. The resulting slurry is centrifuged to remove the excess liquid. The vancomycin crystals obtained from centrifugation of the slurry are reslurried in sodium hydroxide (NaOH) to a pH of approximately 4.5 followed by treatment with KH.sub.2 PO.sub.4 to a pH of approximately 2.0. Vancomycin again crystallizes from the solution. The resulting slurry is centrifuged to separate the crystals from the liquid. The resultant solid is dissolved in water and the mixture is eluted in an ion-exchange column to prepare vancomycin hydrochloride.
European Patent Application, Publication No. 0323150 to Catt et al. discloses an alternate method to precipitate vancomycin in a base solution with a pH of 7.8 to 9.0. At pH's above about 9.0, the base crystallization disclosed in Catt et al. is unsatisfactory because reduced yields and discolored products result; pH's of 8.0 to 8.5 are preferred for the crystallization disclosed by this reference.